This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Genden, E. M. Articles by Molineaux, C. J. Search for Related Content PubMed PubMed Citation Articles by Genden, E. M. Articles by Molineaux, C. J.

Hypertension, Vol 18, 360-365, Copyright © 1991 by American Heart Association

ARTICLES

Inhibition of endopeptidase-24.15 decreases blood pressure in normotensive rats

EM Genden and CJ Molineaux
Department of Pharmacology, Mount Sinai School of Medicine, CUNY, NY 10029.

The potent vasodilatory peptide bradykinin is cleaved at the Phe5-Ser6 bond in vitro by the metalloenzyme endopeptidase-24.15 (E.C.3.4.24.15). We now report that intravenous infusion of N-[1-(R,S)-carboxy-3- phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, a specific active site- directed inhibitor of endopeptidase-24.15, produces an immediate drop in mean arterial pressure of as much as 50 mm Hg in pentobarbital- anesthetized, normotensive rats. Arterial pressure recovers within 5 minutes. The B2 bradykinin antagonist [Arg0,Hyp3,Thi5,8,D-Phe7]- bradykinin attenuates the decrease in mean arterial pressure resulting from treatment with the inhibitor. The endopeptidase-24.15 inhibitor potentiates the hypotensive effect of intravenous bradykinin infusion, increasing the maximal effect of the peptide by 47% and increasing the potency by almost 10-fold, while the response to intra-arterial bradykinin is less affected by the inhibitor. These results support a role for endopeptidase-24.15 in the inactivation of endogenous and exogenous bradykinin and suggest a direct involvement of the enzyme in the control of blood pressure.

This article has been cited by other articles:

				R. A. Skidgel, F. Alhenc-Gelas, and W. B. Campbell Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Prologue: Kinins and related systems. New life for old discoveries Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1886 - H1891. [Full Text] [PDF]

				C. N. Shrimpton, A. I. Smith, and R. A. Lew Soluble Metalloendopeptidases and Neuroendocrine Signaling Endocr. Rev., October 1, 2002; 23(5): 647 - 664. [Abstract] [Full Text] [PDF]

				B. Fabris, R. Candido, M. Carraro, F. Fior, M. Artero, C. Zennaro, M. R. Cattin, A. Fiorotto, M. Bortoletto, C. Millevoi, et al. Modulation of Incipient Glomerular Lesions in Experimental Diabetic Nephropathy by Hypotensive and Subhypotensive Dosages of an ACE Inhibitor Diabetes, November 1, 2001; 50(11): 2619 - 2624. [Abstract] [Full Text] [PDF]

				A. I. Smith, R. A. Lew, C. N. Shrimpton, R. G. Evans, and G. Abbenante A Novel Stable Inhibitor of Endopeptidases EC 3.4.24.15 and 3.4.24.16 Potentiates Bradykinin-Induced Hypotension Hypertension, February 1, 2000; 35(2): 626 - 630. [Abstract] [Full Text] [PDF]

				M. C. Chappell, M. N. Gomez, N. T. Pirro, and C. M. Ferrario Release of Angiotensin-(1-7) From the Rat Hindlimb : Influence of Angiotensin-Converting Enzyme Inhibition Hypertension, January 1, 2000; 35(1): 348 - 352. [Abstract] [Full Text] [PDF]

				S.-I. Kitamura, L. A. Carbini, W. H. Simmons, and A. G. Scicli Effects of aminopeptidase P inhibition on kinin-mediated vasodepressor responses Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1664 - H1671. [Abstract] [Full Text] [PDF]

				U. Hilbers, J. Peters, S. R. Bornstein, F. M. A. Correa, O. Johren, J. M. Saavedra, and M. Ehrhart-Bornstein Local Renin-Angiotensin System Is Involved in K+-Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells Hypertension, April 1, 1999; 33(4): 1025 - 1030. [Abstract] [Full Text] [PDF]

				H. Yu, O. A. Carretero, L. A. Juncos, and J. L. Garvin Biphasic Effect of Bradykinin on Rabbit Afferent Arterioles Hypertension, August 1, 1998; 32(2): 287 - 292. [Abstract] [Full Text] [PDF]

				J. Jirácek, A. Yiotakis, B. Vincent, A. Lecoq, A. Nicolaou, F.édér. Checler, and V. Dive Development of Highly Potent and Selective Phosphinic Peptide Inhibitors of Zinc Endopeptidase 24-15 Using Combinatorial Chemistry J. Biol. Chem., September 15, 1995; 270(37): 21701 - 21706. [Abstract] [Full Text] [PDF]